Abstract
Glycoproteins are formed as the result of enzymatic glycosylation or chemical glycation in the body, and produced in vitro in industrial processes. The covalently attached carbohydrate molecule(s) confer new properties to the protein, including modified stability. In the present study, the structural stability of a glycoprotein form of myoglobin, bearing a glucose unit in the N-terminus, has been compared with its native form by the use of molecular dynamics simulation. Both structures were subjected to temperatures of 300 and 500 K in an aqueous environment for 10 ns. Changes in secondary structures and RMSD were then assessed. An overall higher stability was detected for glycomyoglobin, for which the most stable segments/residues were highlighted and compared with the native form. The simple addition of a covalently bound glucose is suggested to exert its stabilizing effect via increased contacts with surrounding water molecules, as well as a different pattern of interactions with neighbor residues.
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Acknowledgments
This study was supported by the Endocrinology and Metabolism Research Institute and performed in its Modeling and Simulation Lab.
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Fig. S1
Snapshots of native and glycated form of human myoglobin simulations extracted at first and last time points at 500 K. Ribbons are α-helices. (GIF 54 kb)
Fig. S2
Three-dimensional representation of residues located at 4.5 Å of Gly1 in (a) Mb and (b) GMb over time in ten sampled structures. (GIF 122 kb)
(GIF 125 kb)
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Alizadeh-Rahrovi, J., Shayesteh, A. & Ebrahim-Habibi, A. Structural stability of myoglobin and glycomyoglobin: a comparative molecular dynamics simulation study. J Biol Phys 41, 349–366 (2015). https://doi.org/10.1007/s10867-015-9383-2
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DOI: https://doi.org/10.1007/s10867-015-9383-2